3,4-dihydro-2H-pyran → 2,5-Dichloro-N-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidin-4-amine

HRID 1897653Notes

Reaction equation

HRID 1897653 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH3:14])[NH:11][N:10]=2)[C:5]([Cl:15])=[CH:4][N:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:28]1[CH2:33][O:32][CH:31]=[CH:30][CH2:29]1>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH3:14])[N:11]([CH:31]3[CH2:30][CH2:29][CH2:28][CH2:33][O:32]3)[N:10]=2)[C:5]([Cl:15])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 114022722,5-Dichloro-N-(5-methyl-1H-pyrazol-3-yl)-4-pyrimidinamine

Product 1

HCID 582550552,5-Dichloro-N-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidin-4-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2,5-dichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (2.44 g, 10 mmol) and 4-toluenesulfonic acid monohydrate (1.9 g, 10 mmol) in THF (200 mL), was added DHP (4.25 g, 50 mmol). After stirring overnight, the reaction turned clear. After concentration, the residue was dissolved in ethyl acetate and washed with Na2CO3 saturated aqueous solution. The organic layer was then washed with brine, dried over sodium sulfate and concentrated in vacuo to afford 2,5-Dichloro-N-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidin-4-amine as light yellow solid, which was used in subsequent reactions without further purification; ESMS m/z 244 (M−THP+H+); TLC Rf=0.6 (Silica; 1:1 ethyl acetate/hexanes; starting material Rf=0.2).

Workup

  1. concentrationAfter concentration
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed with Na2CO3 saturated aqueous solution
  4. washThe organic layer was then washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3f0416e0959d43d7b38069edf9fbd719
Source dataset
uspto-grants-2013_08
Patent number
US08519129B2

Reaction notes

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